Title page
Full title:
Association of oncogenic and non-oncogenic human
papillomavirus with HIV incidence
Authors
Bertran Auvert, MD, PhD
bertran.auvert@uvsq.fr
INSERM U687, Assistance PubliqueHôpitaux de Paris, University of
Versailles, France
Pascale Lissouba, MS
pascale.lissouba@inserm.fr INSERM U687, France
Ewalde Cutler, MS
ewaldec@nicd.ac.za
National Institute for Communicable
Diseases, Johannesburg, South Africa
Kevin Zarca, MS
kevin.zarca @inserm.fr
INSERM U687, France
Adrian Puren, MD, PhD
adrianp@nicd.ac.za
National Institute for Communicable
Diseases, Johannesburg, South Africa
Dirk Taljaard, PhD
dirk@progressus.co.za
Progressus, Johannesburg, South Africa
Corresponding author
Prof. Bertran Auvert, INSERM U687, 16 avenue Paul Vaillant-Couturier, 94804
Villejuif, France
Tel: +33 1 77 74 74 12 Fax: +33 1 77 74 74 03
bertran.auvert@uvsq.fr
Sources of support
ANRS grant 1265 (France), NICD (South Africa), Bill&Melinda Gates Foundation (USA)
grant 33759 and INSERM (France).
Running head: The HPV-HIV association
2
Abstract/key word page
Association of oncogenic and non-oncogenic human
papillomavirus with HIV incidence
Word count: 199 (max=200)
Objective: Little is known about the interaction between HPV and HIV. This study aimed to
explore the association of oncogenic (HR) and non oncogenic (LR) human papillomavirus
(HPV) with HIV incidence.
Methods: We used urethral swabs collected at the last follow-up visit of a male circumcision
trial conducted in Orange Farm (South Africa). Swabs analyses and HPV genotyping were
performed by polymerase chain reaction. We estimated HIV adjusted incidence rate ratios
(aIRR) and 95% confidence intervals (CI) using survival analysis. Background characteristics,
male circumcision status, sexual behavior, HPV status and other sexually transmitted
infections were used as covariates.
Results: The prevalence of HR and LR HPV was 14.0% (95%CI: 12.4 to 15.7) and 17.3%
(95%CI: 15.6 to 19.2), respectively. When controlling for HR-HPV status, LR-HPV status
was not associated with HIV incidence (aIRR = 1.13, 95%CI: 0.40 to 3.16; P = 0.82). When
controlling for all covariates, HIV incidence increased significantly with HR-HPV positivity
(aIRR=3.76, 95%CI: 1.83 to 7.73, P < 0.001) and with the number of HR-HPV genotypes
(adjusted-P linear trend = 0.0074).
Conclusions: Several explanations could account for our findings. One is that HR-HPV
facilitates HIV acquisition. The association of HPV with HIV acquisition requires further
investigations.
Keywords : HIV; HPV; male circumcision; Africa; men
3
Word count: 2375
Genital human papillomavirus (HPV) genotypes are divided into "high-risk" (HR)
and "low-risk" (LR) genotypes, on the basis of their oncogenic potential.1 LR-HPVs are most
commonly associated with non-malignant lesions such as genital warts,2 while HR-HPV are
found in virtually all pre-malignant or malignant lesions of the genitals and are associated
with cancers of the cervix, vulva, vagina, anus, and penis.1-5
Genital HPV, which is highly infectious, is thought to be vastly prevalent among men
and women in sub-Saharan Africa, and cervical cancer, attributable to HR-HPV at over 99%,
6
is the leading cause of cancer mortality among women in Southern Africa.1 HIV infection is
also correlated with invasive cervical cancer, since it is a recognized AIDS defining condition.
In view of the importance of both infections in the burden of morbidity and mortality in the
region, research on the epidemiologic and etiologic association of HIV and HPV is of great
public health relevance.
Most studies investigating the association between genital HPV and HIV have focused
on the effects of HIV infection on HPV prevalence, incidence and genotype distribution.
Several studies found that HIV positive status was strongly associated with higher HPV
prevalence in men and women,1,7-11 higher HR-HPV prevalence,7,9-13, higher HPV incidence,
14
, higher prevalence of infections with multiple HPV genotypes7-12, and higher frequency of
HPV lesions in multiple locations.12
The objective of this study was to explore the association of HR- and LR-HPV with
HIV incidence. For these analyses, we used longitudinal data collected in Orange Farm
(South Africa), an area of high HIV prevalence,15 during a male circumcision randomized
controlled trial which demonstrated a reducing effect of male circumcision on the acquisition
of HIV.16
METHODS
Collection of data
The technical details of the trial (ANRS-1265) have been published elsewhere.16
Briefly, male participants, aged 18 to 24, were recruited from the general population of the
township of Orange Farm (South Africa) and followed up for 21 months. During each followup visit at 3, 12 and 21 months, data on background information and sexual behavior was
collected, and participants’ circumcision status was assessed by a nurse.
4
As described in previous publications, blood samples collected at each follow-up visit
were tested for HIV and Herpes Simplex Virus type 2 (HSV-2), and urine samples collected
at the 21-month visit were tested for Neisseria gonorrhoeae, Chlamydia trachomatis and
Trichomonas vaginalis.16-18
To conduct HPV testing, a urethral cotton swab, introduced in the first 5 mm of the
urethra, was collected by the same nurse from participants coming for the 21-month visit. For
practical reasons, this collection took place from October 1st, 2005 to November 24th, 2006.
The data used in the current study includes 596 additional follow-up visits which were
collected after the database used to report the results of the trial on HIV incidence
16
was
completed. Furthermore, the database also includes data from the analyses of 490 additional
urethral swabs which were collected from October 1st, 2005 to March 6th, 2005 but were not
used in the report on HR-HPV prevalence among trial participants,19 because they had been
mislaid by the testing laboratory.
Laboratory methods
Swabs specimens for HPV testing were frozen at -20°C immediately after collection
and kept frozen until processing. DNA was extracted from urethral swabs using the MagNA
Pure LC instrument, with the Roche MagNA Pure LC DNA I Isolation Kit (Roche
Diagnostics, Mannheim, Germany). Swabs were lysed in 500 µl of the kit lysis buffer for 30
minutes at room temperature. The MagNa Pure external lysis protocol was used to extract
DNA from the lysis buffer into a 100-µl eluate. 50 µl of the eluate was used for screening
(Roche Amplicor HPV test, Roche Diagnostics, Branchburg, NJ, USA) and 50-µl eluate was
used for genotyping (Roche Linear Array Genotyping test, Roche Diagnostics, Branchburg,
NJ, USA). 14/1771 (0.85%) samples with a negative internal beta-globin PCR control were
excluded. All positive results were genotyped. This standardized PCR-based method can
detect 13 HR-HPV genotypes (i.e., genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59,
and 68) and 24 LR-HPV genotypes (i.e., genotypes 6, 11, 26, 40, 42, 53, 54, 55, 61, 62, 64,
66, 67, 69, 70, 71, 72, 73, 81, 82, 83, 84, IS39 and CP6108). Because of the combined probe
of the assay for HPV-52 and in order to be conservative, samples were classified as HPV-52
positive only when they were negative for genotypes 33, 35 and 58. A HR-HPV sample was
defined as positive if at least one HR-HPV was detected, likewise for LR-HPV. Samples
could be positive for both HR-HPV and LR-HPV. In some analyses, we considered multiple
HR-HPV samples, defined as samples where at least two HR-HPV genotypes were detected.
5
Data analysis
The main analyses were performed on a subset of 1683 participants who were HIVnegative at inclusion and were tested for both HPV and HIV at the 21-month visit. They
represent 1683/2949 (57.1%) of the participants who were tested for HIV at the 21-month
visits. The associations of HR-HPV and LR-HPV statuses with age were tested using logistic
regression, controlling for ethnic group, education, circumcision status and condom use. HIV
incidence rate and HIV incidence rate ratios (IRRs) were estimated among participants by a
piecewise exponential proportional hazards model implemented using univariate log-Poisson
regression.20-22 The effect of LR-HPV status on HIV incidence was tested after controlling for
HR-HPV status. The multivariate effect of HR-HPV status on HIV incidence was estimated
controlling for the following covariates: ethnic group, age, education, number of lifetime
partners, condom use in the past 12 months, circumcision status, HSV-2 status at inclusion,
HSV-2 acquisition during follow-up, and the status at the 21-month visit for the following
sexually transmitted diseases: Neisseria gonorrhoeae, Chlamydia trachomatis and
Trichomonas vaginalis.
To estimate the mean duration between HIV acquisition and swab collection for HPV
testing, the date of HIV acquisition was estimated for each participant as the date at mid point
between the last follow-up visit with an HIV-negative test result and the first follow-up visit
when HIV infection was detected.
The confidence intervals of the percentages were calculated using Bayesian
estimation.23 Statistical analyses were performed using the statistical package SPSS for
Windows version 8 (SPSS, Chicago, Illinois, United States) and R version 2.6.2.24
In two ancillary intention-to-treat analyses, we assessed whether the additional data on
HIV and HPV had any impact, first on the estimated effect of MC on HIV incidence and
secondly on the estimated effect of MC on HPV prevalence. These effects were recalculated
using the methods described in the corresponding publications.16,19
Ethics
The research protocol was reviewed and approved by the University of Witwatersrand
Human Research Ethics Committee (Medical) on February 22nd, 2002 (protocol study no.
M020104). The trial was also approved by the Scientific Commission of the French National
Agency for AIDS Research (ANRS; protocol study no. 1265; 2002, decision No. 50) and
authorization was obtained from the City of Johannesburg, Region 11, on 25 February 2002.
6
This trial has been registered at http://www.clinicaltrials.gov under the number
NCT00122525.
RESULTS
Population characteristics
The background characteristics of the 1683 participants included in this study are
presented in Table 1. The proportion of participants infected with HPV increased with age (Plinear trend=0.0024). The prevalence of HR-HPV was significantly higher than the
prevalence of LR-HPV (P < 0.001, McNemar test). The number of HR-HPV genotypes and
LR-HPV genotypes among those infected with at least one HPV genotype were correlated (P
< 0.001, Spearman's rank correlation test). The prevalences of LR-HPV and HR-HPV were
also correlated (P < 0.001, Fisher's Exact Test). Among the participants infected with a HRHPV, 70.5% (95%CI: 65.2 to 75.6) were also infected with a LR-HPV, and among all those
infected with a LR-HPV, 87.3% (95%CI: 82.7 to 91.1) were also infected with a HR-HPV.
The distributions of HR- and LR-HPV genotypes are listed in Table 2. As shown in this table,
the two most frequent HR-HPV were genotypes 16 and 18 and HPV 6 was by far the most
frequent LR-HPV. After controlling for age, ethnic group, education, circumcision status,
sexually transmitted infections and condom use, HR-HPV and LR-HPV statuses were
significantly associated with number of lifetime partners with P-values for linear trend of
0.025 and 0.022, respectively.
HIV prevalence and incidence
During follow-up, 33/1683 (2.0%) participants became HIV-positive. At the 21-month
follow-up visit, HIV prevalence among those HR-HPV negative was 1.1% (15/1391) and
6.2% (18/292) among those HR-HPV positive (RR=5.72 (2.88-11.3) P < 0.001).
HIV incidence was higher among those with at least one HPV genotype compared to
those with no detected HPV in univariate analysis: 5.26 /100 person-year (py) versus 0.96
/100py; (IRR = 5.45, 95%CI: 2.72 to 10.9; P < 0.001) and when controlling for covariates
(aIRR = 4.55, 95%CI: 2.23 to 9.28; P < 0.001).
When controlling for HR-HPV status, LR-HPV status was not associated with HIV
incidence (aIRR = 1.13, 95%CI: 0.40 to 3.16; P = 0.82) Table 3 indicates the effect of HRHPV status and covariates on HIV incidence. In the univariate and multivariate analyses, HIV
incidence was significantly higher among HR-HPV positive participants. HIV incidence
7
increased with the number of HR-HPV genotypes involved in multiple infections in univariate
analysis (figures 1 & 2). In multivariate analysis, among those positive for at least one HRHPV genotype, HIV incidence increased on average by a factor of 1.55 (95%CI: 1.12 to 2.14;
P = 0.0074) when the number of HR-HPV genotypes increased by one unit.
The mean duration between the estimated date of HIV acquisition and the date of the
swabbing for the detection of HPV was 10.2 months (interquartile range; 4.6 to 13.6 months).
Effect of MC on HIV incidence and on HR-HPV prevalence
With the additional follow-up visits and HIV results, there were 21 HIV infections
(incidence rate 0.82 per 100 person-years) in the intervention group and 52 (2.1 per 100
person-years) in the control group, corresponding to an HIV incidence rate ratio of 0.40
(95%CI: 0.24% to 0.66%; P < 0.001). The prevalences of HR-HPV among the intervention
and control groups were 14.5% (129/890) and 22.1% (191/863), respectively, with a
prevalence ratio of 0.65 (0.52 to 0.82) (P < 0.001). Almost identical estimates were reported
in the initial publications: 0.40 for HIV risk ratio and 0.66 for the HPV prevalence rate
ratio.16,19
DISCUSSION
Using longitudinal data from a male circumcision trial, this study revealed for the first
time a significant association of oncogenic HPV with HIV incidence among African young
men. Conversely, this study did not demonstrate an association of non oncogenic HPV with
HIV incidence.
This study has four limitations. Firstly, as with any observational study, no causal
relationship between HPV and HIV can be concluded from the findings. Secondly, urethral
sampling has been shown to be unaffected by circumcision status,19,25 which is important
when studying samples with circumcised and uncircumcised men as it is the case in this
study. However, it has the disadvantage of underestimating the presence of genital HPV.26,27
This underestimation is not expected to change the positive association with HIV incidence
but it cannot be excluded that the strength of this association may vary with swabbing sites.
Despite this possible underestimation, HR-HPV was the most prevalent sexually transmitted
infections in this population. Thirdly, the collection of genital swabs for HPV testing was
conducted at the last follow-up visit, on average several months after HIV infection. It is
therefore possible that, among the subsets of participants who contracted HR-HPV during
8
follow-up, some got infected with HPV after HIV acquisition. This will tend to dilute the
strength of the association between HPV and HIV. Lastly, HPV lesion detection was not
performed in this study.
Several non-exclusive and plausible explanations could account for our findings.
Firstly, HIV and HPV are sexually transmitted viruses which share the same behavioral risk
factors. However, this association remains strong after controlling for sexual behavioral
covariates. Secondly, the results could be partly due to HIV infection facilitating HPV
acquisition or HPV reactivation from the basal cell layer in the epithelium. This explanation is
unlikely to play a significant role because the men participating in this study were recently
infected with HIV and most likely still had an intact immune system. Thirdly, it could be
argued that HIV- HPV coinfected female partners may have shed HR-HPV more intensively
than HIV-negative women. Indeed, in the case of a depressed immune system, HPV lesions
are more likely to be dysplasic28 and immunodepression can reactivate latent HPV
infection.12,29,30 However, the fact that the average age of the female partners of our study
participants was 3 year older than the median age at first sex in this community, which is
about 1731, makes this last explanation unlikely: the female partners had their sexual debut on
average 3 years earlier, making it unlikely that they already had a depressed immune system
due to HIV infection. Fourthly, the findings could indicate that HR-HPV, but not LR-HPV,
facilitates HIV acquisition.
They are several arguments in favour of the latter explanation. First, there is strong
evidence of a correlation between HIV and HPV statuses, as demonstrated in cross-sectional
studies7-9 Secondly, two other longitudinal studies have shown that HPV facilitates HIV
acquisition among men having sex with men in the US32 and among women in Zimbabwe.33
Interestingly, this last study demonstrates a differential effect between HR-HPV and LR-HPV
on HIV acquisition. Thirdly, HR-HPVs facilitating HIV acquisition is biologically plausible.
The possibility that HR-HPV could increase the susceptibility to HIV infection was
first evoked in 2002.34 The arguments are a) that HR-HPV infection of basal cell epithelia
could lead to an active cell-mediated immune response through the recruitment of
macrophages and T lymphocytes,35,36 which are HIV target cells and may facilitate HIV
acquisition, b) genital HPV could simulate cytokines36,37 which can increase HIV
transcription and replication and c) HPV infection can lead to persisting inflammation and
immune system activation.38 In addition, HR-HPV is more likely to result in a persistent
infection (versus LR-HPV), 39-41 increasing the likelihood of HIV acquisition if there is really
HPV-induced immune activation.
9
While this study cannot give a definite explanation of the association of HPV and HIV
incidence, it provides additional evidence on their strong interaction. Further investigations
are needed, using for example existing longitudinal data such as those collected during the
two other male circumcision trials
42,43
or the data collected during the COL-1492 trial
44
conducted on female sex workers from South Africa. Testing the hypothesis that HR-HPV
facilitates HIV acquisition is a complex endeavor because it requires the demonstration of a
causal association, which may only be evidenced through the evaluation of the efficacy of the
existing HPV vaccines against HIV acquisition with a randomized controlled trial.
10
FIGURE CAPTION
FIGURE 1. Distribution of HIV incidence as a function of the number of high-risk human
papillomavirus genotypes.
py indicates person-year.
The data for the number of HR-HPV from 4 to 8 have been combined. The error bars
represent the 95% confidence interval of the HIV incidence. A 2nd degree polynomial curve
has been fitted to the graphics.
FIGURE 2. Distribution of the number of high risk HPV genotypes among the 1683
participants for those with at least one high risk HPV genotype.
The number of participants with any high risk HPV genotype (82.7%, 1391/1683) is not
represented on the figure.
11
ACKNOWLEDGEMENTS
The sources of funding were ANRS grant 1265 (France), NICD (South Africa), Bill &
Melinda Gates Foundation (USA) grant 33759 and INSERM (France).
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Castellsague X. Natural history and epidemiology of HPV infection and cervical
cancer. Gynecol Oncol 2008;110(3 Suppl 2):S4-7.
Monk BJ, Tewari KS. The spectrum and clinical sequelae of human papillomavirus
infection. Gynecol Oncol 2007;107(2 Suppl 1):S6-13.
Human papillomavirus and HPV vaccines: Technical information for policy-makers
and health professionals. 2007.
Baldwin SB, Wallace DR, Papenfuss MR, Abrahamsen M, Vaught LC, Giuliano AR.
Condom use and other factors affecting penile human papillomavirus detection in men
attending a sexually transmitted disease clinic. Sex Transm Dis 2004;31(10):601-7.
Morris BJ. Why circumcision is a biomedical imperative for the 21(st) century.
Bioessays 2007;29(11):1147-58.
Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV,
Snijders PJ, Peto J, Meijer CJ, Munoz N. Human papillomavirus is a necessary cause
of invasive cervical cancer worldwide. J Pathol 1999;189(1):12-9.
Ng'andwe C, Lowe JJ, Richards PJ, Hause L, Wood C, Angeletti PC. The distribution
of sexually-transmitted Human Papillomaviruses in HIV positive and negative patients
in Zambia, Africa. BMC Infect Dis 2007;7:77.
Ng'ayo MO, Bukusi E, Rowhani-Rahbar A, Koutsky LA, Feng Q, Kwena ZA, Holmes
KK. Epidemiology of human papillomavirus infection among fishermen along Lake
Victoria Shore in the Kisumu District, Kenya. Sex Transm Infect 2008;84(1):62-6.
Safaeian M, Kiddugavu M, Gravitt PE, Gange SJ, Ssekasanvu J, Murokora D, Sklar
M, Serwadda D, Wawer MJ, Shah KV, Gray R. Prevalence and risk factors for
carcinogenic human papillomavirus infections in rural Rakai, Uganda. Sex Transm
Infect 2008;84(4):306-11.
Giuliano AR, Tortolero-Luna G, Ferrer E, Burchell AN, de Sanjose S, Kjaer SK,
Munoz N, Schiffman M, Bosch FX. Epidemiology of human papillomavirus infection
in men, cancers other than cervical and benign conditions. Vaccine 2008;26 Suppl
10:K17-28.
Partridge JM, Koutsky LA. Genital human papillomavirus infection in men. Lancet
Infect Dis 2006;6(1):21-31.
Aynaud O, Piron D, Barrasso R, Poveda JD. Comparison of clinical, histological, and
virological symptoms of HPV in HIV-1 infected men and immunocompetent subjects.
Sex Transm Infect 1998;74(1):32-4.
Mayaud P, Gill DK, Weiss HA, Uledi E, Kopwe L, Todd J, ka-Gina G, Grosskurth H,
Hayes RJ, Mabey DC, Lacey CJ. The interrelation of HIV, cervical human
papillomavirus, and neoplasia among antenatal clinic attenders in Tanzania. Sex
Transm Infect 2001;77(4):248-54.
Safaeian M, Kiddugavu M, Gravitt PE, Gange SJ, Ssekasanvu J, Murokora D, Sklar
M, Serwadda D, Wawer MJ, Shah KV, Gray R. Determinants of incidence and
12
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
clearance of high-risk human papillomavirus infections in rural Rakai, Uganda.
Cancer Epidemiol Biomarkers Prev 2008;17(6):1300-7.
National HIV and syphilis prevalence survey South Africa 2007. Department of
Health, South Africa, 2008;1-47.
Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A.
Randomized, controlled intervention trial of male circumcision for reduction of HIV
infection risk: the ANRS 1265 Trial. PLoS Med 2005;2(11):e298.
Sobngwi-Tambekou J, Taljaard D, Lissouba P, Zarca K, Puren A, Lagarde E, Auvert
B. Effect of HSV-2 Serostatus on Acquisition of HIV by Young Men: Results of a
Longitudinal Study in Orange Farm, South Africa. J Infect Dis 2009.
Sobngwi-Tambekou J, Taljaard D, Nieuwoudt M, Lissouba P, Puren A, Auvert B.
Male circumcision and Neisseria gonorrhoeae, Chlamydia trachomatis and
Trichomonas vaginalis: observations after a randomised controlled trial for HIV
prevention. Sex Transm Infect 2009;85(2):116-20.
Auvert B, Sobngwi-Tambekou J, Cutler E, Nieuwoudt M, Lissouba P, Puren A,
Taljaard D. Effect of male circumcision on the prevalence of high-risk human
papillomavirus in young men: results of a randomized controlled trial conducted in
orange farm, South Africa. J Infect Dis 2009;199(1):14-9.
Frome EL. The analysis of rates using Poisson regression models. Biometrics
1983;39(3):665-74.
Berry G. The analysis of mortality by the subject-years method. Biometrics
1983;39(1):173-84.
Holford TR. The analysis of rates and of survivorship using log-linear models.
Biometrics 1980;36(2):299-305.
Newcombe RG. Two-sided confidence intervals for the single proportion: comparison
of seven methods. Stat Med 1998;17(8):857-72.
Team RDC. R: A language and environment for statistical computing. R Foundation
for Statistical Computing, Vienna, Austria 2005(http://www.R-project.org).
Weaver BA, Feng Q, Holmes KK, Kiviat N, Lee SK, Meyer C, Stern M, Koutsky LA.
Evaluation of genital sites and sampling techniques for detection of human
papillomavirus DNA in men. J Infect Dis 2004;189(4):677-85.
Giuliano AR, Nielson CM, Flores R, Dunne EF, Abrahamsen M, Papenfuss MR,
Markowitz LE, Smith D, Harris RB. The optimal anatomic sites for sampling
heterosexual men for human papillomavirus (HPV) detection: the HPV detection in
men study. J Infect Dis 2007;196(8):1146-52.
Aguilar LV, Lazcano-Ponce E, Vaccarella S, Cruz A, Hernandez P, Smith JS, Munoz
N, Kornegay JR, Hernandez-Avila M, Franceschi S. Human papillomavirus in men:
comparison of different genital sites. Sex Transm Infect 2006;82(1):31-3.
Steben M, Duarte-Franco E. Human papillomavirus infection: epidemiology and
pathophysiology. Gynecol Oncol 2007;107(2 Suppl 1):S2-5.
Aubin F, Pretet JL, Mougin C, Riethmuller D. [Human papillomavirus infection]. Ann
Dermatol Venereol 2007;134(1):94-9.
Strickler HD, Burk RD, Fazzari M, Anastos K, Minkoff H, Massad LS, Hall C, Bacon
M, Levine AM, Watts DH, Silverberg MJ, Xue X, Schlecht NF, Melnick S, Palefsky
JM. Natural history and possible reactivation of human papillomavirus in human
immunodeficiency virus-positive women. J Natl Cancer Inst 2005;97(8):577-86.
Pettifor AE, Rees HV, Kleinschmidt I, Steffenson AE, MacPhail C, HlongwaMadikizela L, Vermaak K, Padian NS. Young people's sexual health in South Africa:
HIV prevalence and sexual behaviors from a nationally representative household
survey. Aids 2005;19(14):1525-34.
13
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
Chin-Hong PV, Husnik M, Cranston RD, Colfax G, Buchbinder S, Da Costa M,
Darragh T, Jones D, Judson F, Koblin B, Mayer KH, Palefsky JM. Anal human
papillomavirus infection is associated with HIV acquisition in men who have sex with
men. Aids 2009;In press.
Smith-McCune K, Chirenje Z, Magure T, Ma Y, Moscicki A, Palefsky J, Chipato T,
Shiboski S, Van der Staten A, Sawaya G. Detection of type-specific cervicovaginal
Human papillomavirus increases the risk of HIV infection independent of other
sexually transmitted infections. CROI 2009: Abstract 516 2009.
Clarke B, Chetty R. Postmodern cancer: the role of human immunodeficiency virus in
uterine cervical cancer. Mol Pathol 2002;55(1):19-24.
Coleman N, Birley HD, Renton AM, Hanna NF, Ryait BK, Byrne M, TaylorRobinson D, Stanley MA. Immunological events in regressing genital warts. Am J
Clin Pathol 1994;102(6):768-74.
Nicol AF, Fernandes AT, Grinsztejn B, Russomano F, JR ES, Tristao A, Perez Mde
A, Nuovo GJ, Martinez-Maza O, Bonecini-Almeida Mda G. Distribution of immune
cell subsets and cytokine-producing cells in the uterine cervix of human
papillomavirus (HPV)-infected women: influence of HIV-1 coinfection. Diagn Mol
Pathol 2005;14(1):39-47.
Gage JR, Sandhu AK, Nihira M, Bonecini-Almeida MdG, Cristoforoni P, Kishimoto
T, Montz FJ, Martinez-Maza O. Effects of human papillomavirus-associated cells on
human immunodeficiency virus gene expression. Obstet Gynecol 2000;96(6):879-85.
Behbahani H, Walther-Jallow L, Klareskog E, Baum L, French AL, Patterson BK,
Garcia P, Spetz AL, Landay A, Andersson J. Proinflammatory and type 1 cytokine
expression in cervical mucosa during HIV-1 and human papillomavirus infection. J
Acquir Immune Defic Syndr 2007;45(1):9-19.
Franco EL, Villa LL, Sobrinho JP, Prado JM, Rousseau MC, Desy M, Rohan TE.
Epidemiology of acquisition and clearance of cervical human papillomavirus infection
in women from a high-risk area for cervical cancer. J Infect Dis 1999;180(5):1415-23.
Brown DR, Shew ML, Qadadri B, Neptune N, Vargas M, Tu W, Juliar BE, Breen TE,
Fortenberry JD. A longitudinal study of genital human papillomavirus infection in a
cohort of closely followed adolescent women. J Infect Dis 2005;191(2):182-92.
Rowhani-Rahbar A, Hawes SE, Sow PS, Toure P, Feng Q, Dem A, Dembele B,
Critchlow CW, N'Doye I, Kiviat NB. The impact of HIV status and type on the
clearance of human papillomavirus infection among Senegalese women. J Infect Dis
2007;196(6):887-94.
Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, Kiwanuka N,
Moulton LH, Chaudhary MA, Chen MZ, Sewankambo NK, Wabwire-Mangen F,
Bacon MC, Williams CF, Opendi P, Reynolds SJ, Laeyendecker O, Quinn TC, Wawer
MJ. Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised
trial. Lancet 2007;369(9562):657-66.
Bailey RC, Moses S, Parker CB, Agot K, Maclean I, Krieger JN, Williams CF,
Campbell RT, Ndinya-Achola JO. Male circumcision for HIV prevention in young
men in Kisumu, Kenya: a randomised controlled trial. Lancet 2007;369(9562):643-56.
Marais DJ, Constant D, Allan B, Carrara H, Hoffman M, Shapiro S, Morroni C,
Williamson AL. Cervical human papillomavirus (HPV) infection and HPV type 16
antibodies in South African women. J Clin Microbiol 2008;46(2):732-9.